Portfolio of compositions with commentaries 2012-2015

This writing forms part of a portfolio of works which gathers together notations and recordings made between 2012 and 2015. The writing divides into four chapters. The first chapter undertakes an examination of abstraction. From the proposition obtained therein, that it is possible to extend within abstraction beyond a correspondence between its terms and concrete manifestations, I ask in what way abstraction may be considered to function therefrom. The second chapter performs an analysis of radical music notations from the nineteenth, twentieth, and twenty-first centuries. The central analysis identifies what is essentially an evolution of what I call ''figuration'' throughout three non-chronological phases of Christian Wolff's notations. The chapter closes by questioning what form of understanding might yet be pursued in respect of this work given (a) its nature, and (b) the nature of our inquiry. The third chapter reflects on some of the philosophical problematics raised in the preceding chapters, at the same time as it prepares for those that follow in the final chapter. The final chapter is a record of the development of my thought appertaining to my compositional work. It sets out two case studies (prepared piano and postcard notations) before proceeding to a selected set of commentaries. Finally, the notion of the functioning of written and acoustical ''marks'' developed in the preceding commentaries is generalised as I develop an aesthetics of scriptural experience.

Participation by place-based community organisations in local development: case studies from East Cork

The past two decades have witnessed concerted efforts by theorists and policy-makers to place civil society at the centre of social, economic and environmental development processes. To this end, policies grounded in a Third Way approach have sought to forge stronger linkages between the state and voluntary community-based organisations. Concepts such as active citizenship, social capital, partnership and sustainability have underpinned this political philosophy, which reflects a movement in development theory and political science away from notions of state-led development and unfettered neo-liberalism. In the Irish context, a series of initiatives have given expression to this new policy agenda, the foremost amongst them the publication of a White Paper in 2000. New local governance structures and development schemes have multiplied since the early 1990s, while the physical planning system has also been modified. All this has taken place against the backdrop of unprecedented economic development and social change precipitated by the ‘Celtic Tiger’.This thesis examines the interaction between community organisations, state institutions and other actors in development processes in East Cork. It focuses upon place-based community organisations, who seek to represent the interests of their particular localities. A case study approach is employed to explore the realpolitik of local development and to gauge the extent to which grassroots community organisations wield influence in determining the development of their communities. The study concludes that the transfer of decision-making power to community organisations has been more illusory than real and that, in practical terms, such groups remain marginal in the circuits of power. However, the situation of community organisations operating in different geographical locales cannot be reduced to an overarching theoretical logic. The case studies show that the modus operandi of community groups varies considerably and can be influenced by specific local geographies, events and personalities.

Living long-term with acquired brain injury in Ireland: towards a counter discourse

Irish literature on Acquired Brain Injury (ABI) is very scant and is mainly deficits and/or needs based. The focus is generally on how to manage the short term needs of the younger population with ABI. The starting position of my thesis is that people living long-term with ABI are important participants in developing knowledge about this social phenomenon, living with ABI while accepting that their brain injury does not determine them. Six mature adults with ABI and their six significant others participated in this longitudinal study. Using a narrative approach in interviews, over twenty months, five repeat individual interviews with each of the twelve participants was held. From this I gained an understanding of their lived experiences, their life-world and their experiences of our local public ABI/disability services, systems and discourse. Along with this new empirical data, theoretical developments from occupational therapy, occupational science, sociology, and disability studies were also used within a meta-narrative informed by critical theory and critical realism to develop a synthesis of this study. Social analysis of their narratives co-constructed with me, allowed me generate nuanced insights into tendencies and social processes that impacted and continues to impact on their everyday-everynight living. I discuss in some depth here, the relational attitudinal, structural, occupational and environmental supports, barriers or discrimination that they face(d) in their search for social participation and community inclusion. Personal recognition of the disabled participants by their family, friends and/or local community, was generally enhanced after much suffering, social supports, slow recovery, and with some form of meaningful occupational engagement. This engagement was generally linked with pre-injury interests or habits, while Time itself became both a major aid and a need. The present local ABI discourse seldom includes advocacy and inclusion in everyday/every night local events, yet most participants sought both peer-support or collective recognition, and social/community inclusion to help develop their own counter-discourse to the dominant ABI discourse. This thesis aims to give a broad social explanation on aspects of their social becoming, 'self-sameness' and social participation, and the status of the disabled participants wanting to live 'the slow life'. Tensions and dialectical issues involved in moving from the category of a person in coma, to person with a disability, to being a citizen should not demote the need for special services. While individualized short-term neuro-rehabilitation is necessary, it is not sufficient. Along with the participants, this researcher asks that community health and/or social care planners and service-providers rethink how ABI is understood and represented, and how people with ABI are included in their local communities

Mainstream technology as an occupational therapy tool: technophobe or technogeek?

Occupational therapists need to embrace the use of mainstream technology in their quest to ensure that therapy remains current and meaningful to their clients. Technology can be useful to improve both functional independence and occupational performance. This opinion piece introduces how occupational therapists can apply mainstream technologies, including information and communication technologies such as the internet, computer software, portable devices and computer games, in their everyday interventions.

A new world a new American foreign policy: the Carter administration, Nicaragua, and the legacy of the Vietnam War, 1977-1981

The impact of the Vietnam War conditioned the Carter administration’s response to the Nicaraguan revolution in ways that reduced US engagement with both sides of the conflict. It made the countries of Latin America counter the US approach and find their own solution to the crisis, and allowed Cuba to play a greater role in guiding the overthrow of Nicaraguan dictator Anastasio Somoza Debayle. This thesis re-evaluates Carter’s policy through the legacy of the Vietnam War, because US executive anxieties about military intervention, Congress’s increasing influence, and US public concerns about the nation’s global responsibilities, shaped the Carter approach to Nicaragua. Following a background chapter, the Carter administration’s policy towards Nicaragua is evaluated, before and after the fall of Somoza in July 1979. The extent of the Vietnam influence on US-Nicaraguan relations is developed by researching government documents on the formation of US policy, including material from the Jimmy Carter Library, the Library of Congress, the National Security Archive, the National Archives and Records Administration, and other government and media sources from the United Nations Archives, New York University, the New York Public Library, the Hoover Institution Archives, Tulane University and the Organization of American States. The thesis establishes that the Vietnam legacy played a key role in the Carter administration’s approach to Nicaragua. Before the overthrow of Somoza, the Carter administration limited their influence in Nicaragua because they felt there was no immediate threat from communism. The US feared that an active role in Nicaragua, without an established threat from Cuba or the Soviet Union, could jeopardise congressional support for other foreign policy goals deemed more important. The Carter administration, as a result, pursued a policy of non-intervention towards the Central American country. After the fall of Somoza, and the establishment of a new government with a left wing element represented by the Sandinistas, the Carter administration emphasised non-intervention in a military sense, but actively engaged with the new Nicaraguan leadership to contain the potential communist influence that could spread across Central America in the wake of the Nicaraguan revolution.

Investigation of global regulators influencing styrene metabolism and bioplastic synthesis in Pseudomonas putida CA-3

The genetics and biochemistry involved in the biodegradation of styrene and the production of polyhydroxyalkanoates in Pseudomonas putida CA-3 have been well characterised to date. Knowledge of the role played by global regulators in controlling these pathways currently represents a critical knowledge gap in this area. Here we report on our efforts to identify such regulators using mini-Tn5 transposon mutagenesis of the P. putida CA-3 genome. The library generated was subjected to phenotypic screening to identify mutants exhibiting a reduced sensitivity to the effects of carbon catabolite repression of aromatic pathway activity. Our efforts identified a clpX disrupted mutant which exhibited wild-type levels of growth on styrene but significantly reduced growth on phenylacetic acid. RT-PCR analysis of key PACoA catabolon genes necessary for phenylacetic acid metabolism, and SDS-PAGE protein profile analyses suggest that no direct alteration of PACoA pathway transcriptional or translational activity was involved. The influence of global regulators affecting the accumulation of PHAs in P. putida CA-3 was also studied. Phenotypic screening of the mini-Tn5 library revealed a gacS sensor kinase gene disruption resulting in the loss of PHA accumulation capacity in P. putida CA-3. Subsequent SDS-PAGE protein analyses of the wild type and gacS mutant strains identified post-transcriptional control of phaC1 synthase as a key point of control of PHA synthesis in P. putida CA-3. Disruption of the gacS gene in another PHA accumulating organism, P. putida S12, also demonstrated a reduction of PHA accumulation capacity. PHA accumulation was observed to be disrupted in the CA-3 gacS mutant under phosphorus limited growth conditions. Over-expression studies in both wild type CA-3 and gacS mutant demonstrated that rsmY over-expression in gacS disrupted P. putida CA-3 is insufficient to restore PHA accumulation in the cell however in wild type cells, over-expression of rsmY results in an altered PHA monomer compositions.

Deer forests, game shooting and landed estates in the South West of Ireland, 1840 - 1970

This thesis is concentrated on the historical aspects of the elitist field sports of deer stalking and game shooting, as practiced by four Irish landed ascendancy families in the south west of Ireland. Four great estates were selected for study. Two of these were, by Irish standards, very large: the Kenmare estate of over 136,000 acres in the ownership of the Roman Catholic Earls of Kenmare, and the Herbert estate of over 44,000 acres in the ownership of the Protestant Herbert family. The other two were, in relative terms, small: the Grehan estate of c.7,500 acres in the ownership of the Roman Catholic Grehan family, and the Godfrey estate of c.5,000 acres, in the ownership of the Protestant Barons Godfrey. This mixture of contrasting estate size, owner's religions, nobleman, minor aristocrat and untitled gentry should, it is argued, yield a diversity of the field sports and lifestyles of their owners, and go some way to assess the contributions, good or bad, they have bequeathed to modern Ireland. Equally, it should help in assessing what importance, if any, applied to hunting. In this context, hunting is here used in its broadest meaning, and includes deer stalking and game shooting, as well as hunting with dogs and hounds on foot and horseback. Where a specific type of hunting is involved, it is so described; for example, fox hunting, stag hunting, hare hunting. Similarly, the term game is sometimes used in sporting literature to encompass all species of quarry killed, and can include deer, ground game (hares and rabbits), waterfowl, and various species of game birds. Where it refers to specific species, these are so described; for example grouse, pheasants, woodcork, wild duck, etc. Since two of these estates - the Kenmare and Herbert - each created a deer forest, unique in mid-19th century Ireland, they form the core study estates; the two smaller estates serve as comparative studies. And, equally unique, as these two larger estates held the only remnant population of native Irish red deer, the survival of that herd itself forms a concomitant core area of analysis. The numerary descriptions applied to these animals in popular literature are critically reassessed against prime source historical evidence, as are the so-called deer forest 'clearances'. The core period, 1840 to 1970, is selected as the seminal period, spanning 130 years, from the creation of the deer forests to when a fundamental change in policy and administration was introduced by the state. Comparison is made with similar estates elsewhere, in Britain and especially in Scotland. Their influence on the Irish methods and style of hunting is historically examined.

Farmers, agriculture and politics in the Irish Free State area, 1919-1936

Given the economic and social importance of agriculture in the early years of the Irish Free State, it is surprising that the development of organisations representing farmers has not received the attention it deserves from historians. While the issues of government agricultural policy and the land question have been extensively studied in the historiography, the autonomous response by farmers to agricultural policies and the detailed study of the farmers’ organisations has simply been ignored in spite of the existence of a range of relevant primary sources. Farmers’ organisations have only received cursory treatment in these studies; they have been presented as passive spectators, responding in a Pavlovian manner to outside events. The existing historiography has only studied farmers’ organisations during periods when they impinged on national politics, epecially during the War of Independence and the Economic War. Therefore chronological gaps exist which has led to much misinterpretation of farmers’ activities. This thesis will redress this imbalance by studying the formation and continuous development of farmers’ organisations within the twenty-six county area and the reaction of farmers to changing government agricultural policies, over the period 1919 to 1936. The period under review entailed many attempts by farmers to form representative organisations and encompassed differing policy regimes. The thesis will open in 1919, when the first national organisation representing farmers, the Irish Farmers’ Union, was formed. In 1922, the union established the Farmers’ Party. By the mid- 1920’s, a number of protectionist agricultural associations had been formed. While the Farmers’ Party was eventually absorbed by Cumann na nGaedheal, local associations of independent farmers occupied the resultant vacuum and contested the 1932 election. These organisations formed the nucleus of a new national organisation; the National Farmers’ and Ratepayers’ League. The agricultural crisis caused by both the Great Depression and the Economic War facilitated the expansion of the league. The league formed a political party, the Centre Party, to contest the 1933 election. While the Centre Party was absorbed by the newly-formed Fine Gael, activists from the former farmer organisations led the campaign against the payment of annuities and rates. Many of them continued this campaign after 1934, when the Fine Gael leadership opposed the violent resistance to the collection of annuities. New farmer organisations were formed to co-ordinate this campaign which continued until 1936, the closing point of the thesis.

Targeting the EP1 receptor reduces Fas ligand expression and increases the antitumor immune response in an in vivo model of colon cancer

Despite studies demonstrating that inhibition of cyclooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) has significant chemotherapeutic benefits in vitro and in vivo, inhibition of COX enzymes is associated with serious gastrointestinal and cardiovascular side effects, limiting the clinical utility of these drugs. PGE2 signals through four different receptors (EP1–EP4) and targeting individual receptor(s) may avoid these side effects, while retaining significant anticancer benefits. Here, we show that targeted inhibition of the EP1 receptor in the tumor cells and the tumor microenvironment resulted in the significant inhibition of tumor growth in vivo. Both dietary administration and direct injection of the EP1 receptor-specific antagonist, ONO-8713, effectively reduced the growth of established CT26 tumors in BALB/c mice, with suppression of the EP1 receptor in the tumor cells alone less effective in reducing tumor growth. This antitumor effect was associated with reduced Fas ligand expression and attenuated tumor-induced immune suppression. In particular, tumor infiltration by CD4+CD25+Foxp3+ regulatory T cells was decreased, whereas the cytotoxic activity of isolated splenocytes against CT26 cells was increased. F4/80+ macrophage infiltration was also decreased; however, there was no change in macrophage phenotype. These findings suggest that the EP1 receptor represents a potential target for the treatment of colon cancer.

Novel coatings for hard tissue implants

A novel deposition process named CoBlastTM, based on grit blasting technology, has been used to deposit hydroxyapatite (HA) onto titanium (Ti) metal using a dopant/abrasive regime. The various powders (HA powder, apatitic abrasives) and the treated substrates were characterised for chemical composition, coating coverage, crystallinity and topography including surface roughness. The surface roughness of the HA surfaces could be altered using apatitic abrasives of different particle sizes. Compared to the standard plasma spraying process, the CoBlast surface produced excellent coating adhesion, lower dissolution, higher levels of mechanical and chemical stability in stimulated body fluid (SBF). Enhanced viability of osteoblastic cells was also observed on the CoBlast HA surfaces compared to the microblast and untreated Ti as well as the plasma HA coating. CoBlast offers an alternative to the traditional methods of coating HA implants with added versatility. Apatites substituted with antimicrobial metals can also be deposited to add functionality to HA coatings without cytotoxicty. The potential use of these coatings as an infection preventing strategy for application on hard tissue implants was assessed in vitro and also in vivo. Surface physicochemical properties and morphology were determined in addition to surface cytocompatibility assessments using a MG-63 osteoblast cell line. The antibacterial potential of the immobilised metal ion on the surface and the eluted ion to a lesser extent, contributed to the anticolonising behaviour of the surfaces against a standard bacteria strain (S. aureus) as well as a number of clinically relevant strains (MRSA, MSSA and S. epidermis). The results revealed that the surfaces coated with silver substituted apatites (AgA) outperformed the other apatites examined (apatites loaded with Zn, Sr and both Ag and Sr ions). Assessment of bacterial adherence on coated K-wires following subcutaneous implantation in a nude mouse infection model (S. aureus) for two days demonstrated that the 12% wt surface outperformed the 5% wt AgA coating. Lower inflammatory responses were activated with the insertion of the Ag loaded K-wires with a localised infection at the implantation site noted over the two day study period. These results indicated that the AgA coating on the surface of orthopaedic implants demonstrate good biocompatibility whilst inhibiting bacterial adhesion and colonising of the implant surface.

The role of the IL-1 type 1 receptor in the life, death and differentiation of adult hippocampal neural precursor cells

Neurogenesis occurs in two distinct regions of the adult brain; the subgranular zone (SGZ) of the dentate gyrus (DG) in the hippocampus, and the subventricular zone (SVZ) lining the lateral ventricles. It is now well-known that adult hippocampal neurogenesis can be modulated by a number of intrinsic and extrinsic factors e.g. local signalling molecules, exercise, environmental enrichment and learning. Moreover, levels of adult hippocampal neurogenesis decrease with age, at least in rodents, and alterations in hippocampal neurogenesis have been reported in animal models and human studies of neuropsychiatric and neurodegenerative conditions. Neuroinflammation is a common pathological feature of these conditions and is also a potent modulator of adult hippocampal neurogenesis. Recently, the orphan nuclear receptor TLX has been identified as an important regulator of adult hippocampal neurogenesis as its expression is necessary to maintain the neural precursor cell (NPC) pool in the adult DG. Likewise, exposure of animals to voluntary exercise has been consistently demonstrated to promote adult hippocampal neurogenesis. Lentivirus (LV)- mediated gene transfer is a useful tool to elucidate gene function and to explore potential therapeutic candidates across an array of conditions as it facilitates sustained gene expression in both dividing and post-mitotic cell populations. Both intrinsic and extrinsic factors are important regulators of adult hippocampal neurogenesis. Examining how these factors are affected by an inflammatory stimulus, and the subsequent effects on adult hippocampal neurogenesis provides important information for the development of novel treatment strategies for neuropsychiatric and neurodegenerative conditions in which adult hippocampal neurogenesis is impaired. The aims of the series of experiments presented in this thesis were to examine the effect of the pro-inflammatory cytokine interleukin-1β (IL-1β) on adult hippocampal NPCs both in vitro and in vivo. In vitro, we have shown that IL-1β reduces proliferation of adult hippocampal NPCs in a dose and time-dependent manner. In addition, we have demonstrated that TLX expression is reduced by IL-1β. Blockade of IL-1β signalling prevented both the IL-1β-induced reduction in cell proliferation and TLX expression. In vivo, we examined the effect of short term and long term exposure to LV-IL-1β in sedentary mice and in mice exposed to voluntary running. We demonstrated that impaired hippocampal neurogenesis is only evident after long term exposure to IL-1β. In mice exposed to voluntary running, hippocampal neurogenesis is significantly increased following short-term but not long-term exposure to running. Moreover, short-term running effectively prevents any IL-1β-induced effects on hippocampal neurogenesis; however, no such effects are seen following long-term exposure to running.

Nutraceutical and functional food bioactive peptides in beef

In recent years, the potential to positively modulate human health through dietary approaches has received considerable attention. Bioactive peptides which are released during the hydrolysis or fermentation of food proteins or following digestion may exert beneficial physiological effects in vivo. The aim of this work was to isolate, characterise and evaluate Angiotensin-І-converting enzyme (ACE-І) inhibitory, antimicrobial and antioxidant peptides from the bovine myofibrillar proteins actin and myosin. In order to generate these peptides, the myofibrillar proteins actin and myosin were hydrolysed with digestive enzymes pepsin, trypsin and α-chymotrypsin, or with the industrial thermolysin-like enzyme “Thermoase”, Amano Inc. It was found that each hydrolysate generated contained peptides which possessed ACE inhibitory, antioxidant and antimicrobial activity. The peptides responsible in part for the observed ACE inhibitory, antioxidant and antimicrobial activity of a number of hydrolysates were isolated using the method of RP-HPLC and the bioactive peptides contained within each active fraction was determined using either MALDI-TOF MS/MS or N-terminal peptide sequencing. During the course of this thesis six ACE inhibitory and five antimicrobial peptides were identified. It was determined that the reported antioxidant activity was a direct result of a number of peptides working in synergy with each other. The IC50 values of the six ACE inhibitory peptides ranged in values of 6.85 to 75.7 µM which compare favourably to values previously reported for other food derived ACE inhibitory peptides, particularly the well known milk peptides IPP and VPP, IC50 values of 5 and 9 µM respectively. All five antimicrobial peptides identified in this thesis displayed activity against Escherichia coli, Salmonella typhimurium, Staphylococcus aureus and Listeria innocua with MIC values ranging from 0.625 to10 mM. The activity of each antimicrobial peptide was strain specific. Furthermore the role and importance of charged amino acids to the activity of antimicrobial peptides was also determined. Generally the removal of charged amino acids from the sequence of antimicrobial peptides resulted in a loss of antimicrobial activity. In conclusion, this thesis revealed that a range of bioactive peptides exhibiting ACE inhibitory, antioxidant and antimicrobial activities were encrypted in bovine myofibrillar proteins that could be released using digestive and industrial enzymes. Finally enzymatic hydrolysates of muscle proteins could potentially be incorporated into functional foods; however, the potential health benefits would need to be proven in human clinical studies.

Application of mesoporous silica for the oral delivery of poorly water-soluble drugs

The objective of this thesis was to improve the dissolution rate of the poorly waters-soluble drug, fenofibrate by processing it with a high surface area carrier, mesoporous silica. The subsequent properties of the drug – silica composite were studied in terms of drug distribution within the silica matrix, solid state and release properties. Prior to commencing any experimental work, the properties of unprocessed mesoporous silica and fenofibrate were characterised (chapter 3), this allowed for comparison with the processed samples studied in later chapters. Fenofibrate was a highly stable, crystalline drug that did not adsorb moisture, even under long term accelerated storage conditions. It maintained its crystallinity even after SC-CO2 processing. Its dissolution rate was limited and dependent on the characteristics of the particular in vitro media studied. Mesoporous silica had a large surface area and mesopore volume and readily picked up moisture when stored under long term accelerated storage conditions (75% RH, 40 oC). It maintained its mesopore character after SC-CO2 processing. A variety of methods were employed to process fenofibrate with mesoporous silica including physical mixing, melt method, solvent impregnation and novel methods such as liquid and supercritical carbon dioxide (SC-CO2) (chapter 4). It was found that it was important to break down the fenofibrate particulate structure to a molecular state to enable drug molecules enter into the silica mesopores. While all processing methods led to some increase in fenofibrate release properties; the impregnation, liquid and SC-CO2 methods produced the most rapid release rates. SC-CO2 processing was further studied with a view to optimising the processing parameters to achieve the highest drug-loading efficiency possible (chapter 5). In this thesis, it was that SC-CO2 processing pressure had a bearing on drug-loading efficiency. Neither pressure, duration or depressurisation rate affected drug solid state or release properties. The amount of drug that could be loaded onto to the mesoporous silica successfully was also investigated at different ratios of drug mass to silica surface area under constant SC-CO2 conditions; as the drug – silica ratio increased, the drug-loading efficiency decreased, while there was no effect on drug solid state or release properties. The influence of the number of drug-loading steps was investigated (chapter 6) with a view to increasing the drug-loading efficiency. This multiple step approach did not yield an increase in drug-loading efficiency compared to the single step approach. It was also an objective in this chapter to understand how much drug could be loaded into silica mesopores; a method based on the known volume of the mesopores and true density of drug was investigated. However, this approach led to serious repercussions in terms of the subsequent solid state nature of the drug and its release performance; there was significant drug crystallinity and reduced release extent. The impact of in vitro release media on fenofibrate release was also studied (chapter 6). Here it was seen that media containing HCl led to reduced drug release over time compared to equivalent media not containing HCl. The key findings of this thesis are discussed in chapter 7 and included: 1. Drug – silica processing method strongly influenced drug distribution within the silica matrix, drug solid state and release. 2. The silica surface area and mesopore volume also influenced how much drug could be loaded. It was shown that SC-CO2 processing variables such as processing pressure (13.79 – 41.37 MPa), duration time (4 – 24 h) and depressurisation rate (rapid or controlled) did not influence the drug distribution within the SBA- 15 matrix, drug solid state form or release. Possible avenues of research to be considered going forward include the development and application of high resolution imaging techniques to visualise drug molecules within the silica mesopores. Also, the issues surrounding SBA-15 usage in a pharmaceutical manufacturing environment should be addressed.

Representations of Catholicism in selected works by Colm Tóibín

The aim of this thesis is to provide an original and extensive study of Colm Tóibín as the “secular revisionist who acknowledges Catholicism as an enduring element of Irish society” (Ryan, Ireland and Scotland 251). Tóibín is uniquely placed to interpret many aspects of Ireland in the latter half of the twentieth century and I will argue that intertwined with his revisionism of Irish history is a reimagining of Ireland and Catholicism in fictive terms. An extensive amount of material from Tóibín’s time as a journalist and travel writer will feature in my research because it validates my argument concerning his prolonged engagement with Catholicism. Similarly, a broad range of Tóibín’s prose will be studied because it affords opportunities for an exploration of a literary Catholic oeuvre in his fiction. Therefore, I am emphasizing that a crucial linkage of Catholicism is identifiable throughout Tóibín’s diverse canon of work. However, I will argue that divergences of attitude and mode can be found in how Tóibín depicts Catholicism in his journalism and fiction. My argument identifies Tóibín’s recurrent journalistic questioning of the Church’s teaching and leadership but I classify a benignity towards Catholicism in his travel writing and fiction. Overall, Tóibín’s fiction merits significant status in this thesis because of the representations of Catholicism in the work of a writer who has been short-listed three times for The Booker Prize.

The role of bacterial interspecies communication in polymicrobial infection of the cystic fibrosis lung

There is an increasing appreciation of the polymicrobial nature of bacterial infections associated with Cystic Fibrosis (CF) and of the important role for interactions in influencing bacterial virulence and response to therapy. Patients with CF are co-infected with Pseudomonas aeruginosa, Burkholderia cenocepacia and Stenotrophomonas maltophilia. These latter bacteria produce signal molecules of the diffusible signal factor (DSF) family, which are cis-2-unsaturated fatty acids. Previous studies showed that DSF from S. maltophilia leads to altered biofilm formation and increased tolerance to antibiotics in P. aeruginosa and that these responses require the P. aeruginosa sensor kinase PA1396. The work in this thesis aims of further elucidate the influence and mechanism of DSF signalling on P. aeruginosa and examine the role that such interspecies signalling play in infection of the CF airway. Next generation sequencing technologies targeting the 16S ribosomal RNA gene were applied to DNA and RNA isolated from sputum taken from cohorts of CF and non-CF subjects to characterise the bacterial community. In parallel, metabolomics analysis of sputum provided insight into the environment of the CF airway. This analysis revealed a number of observations including; that differences in metabolites occur in sputum taken from clinically stable CF patients and those with exacerbation and DNA- and RNA-based methods suggested that a strong relationship existed between the abundance of specific strict anaerobes and fluctuations in the level of metabolites during exacerbation. DSF family signals were also detected in the sputum and a correlation with the presence of DSFproducing organisms was observed. To examine the signal transduction mechanisms used by P. aeruginosa, bioinformatics with site directed mutagenesis were employed to identify signalling partners for PA1396. A pathway suggesting a role for a number of proteins in the regulation of several factors following DSF recognition by PA1396 were observed.